This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HIV and SIV have evolved alternative countermeasures to overcome restriction by tetherin, an interferon-inducible cellular factor that inhibits the release of virus particles from infected cells. We identified compensatory genetic changes in a pathogenic derivative of a nef-deleted vaccine strain of simian immunodeficiency virus that restore resistance to tetherin. These observations suggest that the ability to overcome restriction by tetherin is important for AIDS-virus pathogenesis.